Blood T Helper Memory Cells: A Tool for Studying Skin Inflammation in HS?

Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful lesions on intertriginous body areas such as the axillary, inguinal, and perianal sites. Given the limited treatment options for HS, expanding our knowledge of its pathogenetic mechanisms is a prerequisite for novel therapeutic developments. T cells are assumed to play a crucial role in HS pathogenesis. However, it is currently unknown whether blood T cells show specific molecular alterations in HS. To address this, we studied the molecular profile of CD4⁺ memory T (Th_mem) cells purified from the blood of patients with HS and matched healthy participants. About 2.0% and 1.9% of protein-coding transcripts were found to be up- and down-regulated in blood HS Th_mem cells, respectively. These differentially expressed transcripts (DETs) are known to be involved in nucleoside triphosphate/nucleotide metabolic processes, mitochondrion organization, and oxidative phosphorylation. The detected down-regulation of transcripts involved in oxidative phosphorylation suggest a metabolic shift of HS Th_mem cells towards glycolysis. The inclusion of transcriptome data from skin from HS patients and healthy participants in the analyses revealed that in HS skin lesions, the expression pattern of transcripts identified as DETs in blood HS Th_mem cells was very similar to the expression pattern of the totality of protein-coding transcripts. Furthermore, there was no significant association between the extent of the expressional changes in the DETs of blood HS Th_mem cells and the extent of the expressional changes in these transcripts in HS skin lesions compared to healthy donor skin. Additionally, a gene ontology enrichment analysis did not demonstrate any association of the DETs of blood HS Th_mem cells with skin disorders. Instead, there were associations with different neurological diseases, non-alcoholic fatty liver disease, and thermogenesis. The levels of most DETs linked to neurological diseases showed a positive correlation to each other, suggesting common regulatory mechanisms. In summary, the transcriptomic changes in blood Th_mem cells observed in patients with manifest cutaneous HS lesions do not appear to be characteristic of the molecular changes in the skin. Instead, they could be useful for studying comorbidities and identifying corresponding blood biomarkers in these patients.